PDC-TREM, a plasmacytoid dendritic cell-specific receptor, is responsible for augmented production of type I interferon
PDC-TREM, a plasmacytoid dendritic cell-specific receptor, is responsible for augmented production of type I interferon
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DOI：
10.1073/pnas.0710351105
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发表时间：
2008-02-26
影响因子：
11.1
通讯作者：
Taniguchi, Masaru
中科院分区：
文献类型：
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作者：
Watarai, Hiroshi;Sekine, Etsuko;Taniguchi, Masaru
来源于浆细胞样树突状细胞(PDCs)的I型干扰素(IFN)对抗病毒反应至关重要；然而，其产生的机制尚不清楚。我们已经鉴定出一种受体PDC-TREM，它与PDC细胞表面的Plexin-A1(PLXNA1)相关，并在TLR刺激后优先表达。有限的TLR信号可诱导PDC-TREM表达，但不能诱导干扰素-α的产生。然而，当与丛蛋白A1的配体Sema6D结合时，有限的TLR刺激导致PDC-TREM介导的DAP12依赖的磷脂酰肌醇3-激酶(PI3K)和细胞外调节激酶(Erk)1/2在6-9h被磷酸化，并产生干扰素-α。Pdctrem-shRNA抑制PDC-Trem的表达，PDCTREM mAb阻断PDC-Trem与PLXNA1的结合，DAP12缺乏均可显著降低PDC-Trem依赖的信号分子的激活和干扰素-α的产生。因此，PDC-TREM负责产生干扰素-α，而TLR信号是PDC-TREM表达所必需的。
Type I interferons (IFNs) derived from plasmacytoid dendritic cells (PDCs) are critical for antiviral responses; however, the mechanisms underlying their production remain unclear. We have identified a receptor, PDC-TREM, which is associated with Plexin-A1 (PlxnA1) on the PDC cell surface and is preferentially expressed after TLR-stimulation. Limited TLR signals induced PDC-TREM expression but failed to induce IFN-alpha production. However, when coupled with Sema6D, a ligand for Plexin-A1, limited TLR-stimulation resulted in PDC-TREM-mediated DAP12-dependent phosphorylation of phosphoinositide 3-kinase (PI3K) and extracellular regulated kinase (Erk) 1/2 at 6-9 h, and IFN-alpha was produced. Inhibition of PDC-TREM expression by pdctrem-shRNA, blocking of PDC-TREM-binding with PlxnA1 by PDCTREM mAb, and DAP12 deficiency all resulted in greatly reduced PDC-TREM-dependent activation of signaling molecules and IFN-alpha production. Thus, PDC-TREM is responsible for IFN-alpha production, whereas TLR signals are essential for PDC-TREM expression.